# Clinical and Molecular Epidemiology of High Risk Coronary Plaque

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $610,178

## Abstract

Although current practice focuses largely on the detection and management of obstructive
coronary artery disease (CAD), there is marked heterogeneity in the relationship between CAD
and risk for cardiovascular (CV) events. Some patients, despite having obstructive CAD, do not
experience cardiovascular events, while others with non-obstructive CAD do. The mechanisms
of this high risk coronary plaque (HRCP) development are incompletely understood; application
of emerging imaging and molecular technologies holds great promise for simultaneously
identifying underlying biological pathways, markers for early noninvasive detection, and novel
therapeutic targets for HRCP. Thus, we propose to (1) determine the role of inflammation and
other candidate biological pathways in the pathophysiology of HRCP; (2) identify novel
biological pathways mediating development of HRCP through machine learning analyses of
integrated metabolomic, proteomic and transcriptomic profiling; and (3) determine the
incremental prognostic value of these imaging and molecular biomarkers over clinical
factors and create an integrated clinico-molecular model of CV event risk prediction. We will
accomplish these goals by, for the first time, integrating advanced CTA-based phenotyping of
HRCP with molecular profiling and adjudicated CV events, leveraging the robust, existing
resources of a large, unique NIH-funded clinical trial of imaging in chest pain patients
(PROMISE). This proposal holds great public health significance by augmenting current
population- and ischemia- based approaches and more precisely and preemptively identifying
those patients at highest risk. Our findings will provide a critical foundation for the development
of diagnostics and therapeutics targeted at specific, culprit atherosclerotic phenotypes and
molecular pathways.

## Key facts

- **NIH application ID:** 10459303
- **Project number:** 5R01HL146145-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Pamela Susan Douglas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $610,178
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459303

## Citation

> US National Institutes of Health, RePORTER application 10459303, Clinical and Molecular Epidemiology of High Risk Coronary Plaque (5R01HL146145-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10459303. Licensed CC0.

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